Phase 2
N=77
SB-681323 IV for Subjects at Risk of Acute Lung Injury or ARDS
Lung Injury, Acute
Bottom Line
View on ClinicalTrials.gov: NCT00996840 ↗Enrolled (actual)
77
Serious AEs
9.1%
Results posted
Oct 2017
Primary outcome: Primary: Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count — 0.0305; 0.0163; 0.0208; 0.0153 Giga cells per liter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- SB-681323 Intravenous 3mg (Drug); SB-681323 Intravenous 7.5 mg (Drug); SB-681323 Intravenous 7.5mg (Drug); SB-681323 Intravenous 10mg (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Feb 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell Count |
0.0305; 0.0163; 0.0208; 0.0153; 0.0258; 0.0291 | — |
| PRIMARY Mean Hematology Parameters- Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) |
100.8; 97.0; 97.8; 88.4; 97.2; 90.6 | — |
| PRIMARY Mean Hematology Parameters- Mean Corpuscle Hemoglobin |
30.46; 30.74; 30.11; 30.18; 31.10; 30.21 | — |
| PRIMARY Hematology Parameters-Mean Corpuscle Volume |
89.30; 89.59; 88.33; 89.15; 90.63; 89.85 | — |
| PRIMARY Mean Hematology Parameters-reticulocytes, Red Blood Cell Count |
0.0488; 0.0411; 0.0406; 0.0398; 0.0513; 0.0554 | — |
| PRIMARY Mean Clinical Chemistry Parameters- Albumin and Total Protein |
25.2; 25.1; 23.7; 26.2; 24.7; 22.8 | — |
| PRIMARY Mean Clinical Chemistry Parameters-alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase and Gamma Glutamyl Transferase |
52.0; 53.8; 43.5; 49.4; 52.2; 52.6 | — |
| PRIMARY Mean Clinical Chemistry Parameters- Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid |
4.500; 4.275; 8.705; 5.985; 3.306; 4.590 | — |
| PRIMARY Mean Clinical Chemistry Parameters- Calcium, Chloride, Glucose, Bicarbonate, Potassium, Sodium and Ratio of Urea to Blood Urea Nitrogen (Urea/BUN) |
1.9523; 1.9274; 1.9098; 1.9489; 1.9655; 1.9523 | — |
| PRIMARY Mean Clinical Chemistry Parameters-estradiol |
165.150; 210.108 | — |
| PRIMARY Mean Clinical Chemistry Parameters-Blood pH at Screening |
7.358; 7.363; 7.358; 7.353; 7.373 | — |
| PRIMARY Vital Parameter- Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
127.9; 116.6; 130.4; 126.4; 114.8; 130.3 | — |
| PRIMARY Vital Parameter: Mean Heart Rate |
92.7; 89.7; 97.8; 99.8; 93.8; 98.1 | — |
| PRIMARY Vital Sign: Mean Percent Oxygen (O2) in Blood |
98.6; 97.1; 97.6; 97.5; 97.3; 97.3 | — |
| PRIMARY Vital Signs: Mean Oxygen Saturation (SaO2) Via Pulse Oximetry |
— | — |
| PRIMARY Vital Signs: Mean Level of Positive End Expiratory Pressure |
— | — |
| PRIMARY Vital Signs: Mean Level of Peak and Plateau Ventilator Pressures |
— | — |
| PRIMARY Vital Signs: Mean Oxygen Requirement (FiO2) Via Pulse Oximetry |
— | — |
| PRIMARY Mean Electrocardiogram (ECG) Parameters Including PR, QRS, QT, and QTcB, QTcF, RR Intervals |
141.4; 145.5; 141.5; 143.9; 152.9; 145.7 | — |
| PRIMARY Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) |
18; 7; 10; 16; 14; 1 | — |
| SECONDARY Mean Serum Interleukin-6 Levels |
509.44; 286.17; 391.09; 309.57; 395.09; 516.49 | — |
| SECONDARY Mean Serum CXCL8 (Interleuin-8) Levels |
37.66; 18.22; 27.34; 21.06; 21.85; 26.53 | — |
| SECONDARY Mean Serum C-Reactive Protein (CRP) Levels |
123.62; 95.60; 117.68; 117.42; 110.88; 138.02 | — |
| SECONDARY Markers of Endothelial Cell/Neutrophil Interaction: Mean Soluble Tumor Necrosis Factor Receptors-I |
2457.23; 2089.11; 2240.84; 2046.04; 2267.35; 2448.86 | — |
| SECONDARY Markers of Lung Epithelial Cell Injury: Mean Myeloperoxidase (MPO) Levels |
66792.4; 56739.7; 63552.3; 44668.1; 62108.1; 94963.6 | — |
| SECONDARY Mean Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) |
103.222; 186.326; 178.807; 217.862; 112.199; 207.050 | — |
| SECONDARY Mean Average Concentration (Cavg) of SB-681323 |
4.301; 7.764; 7.450; 9.078; 4.675; 8.627 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of SB-681323 |
21.238; 8.519; 38.032; 10.044; 22.830; 8.842 | — |
Summary
This is an early phase (Phase IIa), randomized, double-blind, parallel group, multi-centre study for subjects with trauma (physical injury) who are at risk for developing Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). The primary purpose of the study is to evaluate the safety and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha (MAPK) (prevents inflammation of tissue), in comparison to a placebo.
Eligibility Criteria
Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Male or female, 18 - 80 years of age (inclusive) with major trauma admitted to the Intensive Care Unit (ICU).
- Injury Severity score (ISS) >16 to 3), liver trauma (AIS>2), or trauma that in the opinion of the Principle Investigator or GSK medical monitor is deemed unsurvivable.
- Known history of neuromuscular disease or cord injury at C5 or above.
- Elevated ALT or AST > 1.5 ULN.
- History of bone marrow or solid organ transplant.
- Known history of auto-immune disorder in which immunosuppressive agents, other than prednisone, were required within the last 6 weeks.
- Known to be receiving oral or intravenous corticosteroids within 7 days of admission.
- Subject with active tuberculosis or being treated for active tuberculosis.
- Known history of malignancy within the past 5 years with the exception of successfully treated squamous cell or basal cell cancer of the skin.
- Arterial blood pH less than 7.1 or serum HCO3 - <15 before infusion is started.
- Persistent cardiovascular instability requiring therapy with more than one vasopressor.
- A patient will be excluded if in the judgement of the Principle Investigator or GSK medical monitor their participation could jeopardize the health of the subject or the integrity of the study.
Data sourced from ClinicalTrials.gov (NCT00996840). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.